Skin Substitutes and Wound Healing: Current Status and Challenges

David Eisenbud, MD, CWS; Ngan F. Huang, BS; Sunny Luke, DSc; Melvin Silberklang, PhD


Wounds. 2004;16(1) 

In This Article

History of Skin Transplantation

Autologous skin grafts have been used for more than two thousand years, apparently beginning in India; the first scientific reports come from nineteenth century Europe.[24,25] Cadaver skin has also been used extensively, especially over the past thirty years, mostly in treating extensive burns.[26] Prompt wound coverage is thereby achieved in patients with limited sites for harvesting autologous skin grafts. Typically the allograft is harvested within a day after death and is cryopreserved at liquid nitrogen temperature. While allograft skin will ultimately require excision and autologous regrafting, it may adhere well to the wound for up to several weeks before clinically obvious rejection occurs. Nevertheless, although results with cadaver skin for burn coverage are good, problems with availability, expense, potential disease transmission and questions about the detrimental effects of the cryopreservation process have all limited its use. In answer to the limited availability of cadaver skin, xenograft[27,28] (most often porcine or bovine) skin has also been tested extensively over the years. Results are similar to those with allograft in that initial take is often observed when grafted onto a clean, debrided wound, and angiogenesis is encouraged, albeit with ultimate rejection and the requirement for removal within a few days to a few weeks.

Grafting of cultured cells as skin replacements did not become a clinical reality until the work of O'Connor, et al., who were the first to deliver autologous keratinocyte sheets to burn patients in 1981.[9] The major technological advancement which presaged O'Connor's clinical success was the development of an in-vitro keratinocyte expansion technique by Rheinwald and Green in 1975[8] that paved the way for culturing sheets of autologous keratinocytes.[29] Other researchers have used both autologous fibroblasts and keratinocytes to create composite autologous skin substitutes for burn wound closure.[30] Such successes notwithstanding, the advantage of off-the-shelf availability and the greater commercial potential has led to much more effort in the industrial sector toward the use of allogeneic donor cells to create tissue engineered skin substitutes.


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